Novartis remibrutinib Phase III trials met their primary endpoints and showed rapid symptom control in chronic spontaneous urticaria

Ad hoc announcement pursuant to Art. 53 LR

• The Phase III REMIX-1 and REMIX-2 studies met all primary and secondary endpoints, showing rapid, clinically meaningful improvements across urticaria disease activity scores1

• Patients on remibrutinib saw rapid improvement as early as 2 weeks after treatment initiation1

• Remibrutinib, a highly selective oral BTK inhibitor, was well-tolerated and demonstrated a favorable safety profile, including balanced liver function tests in active and placebo arms across both studies1

• Final (52 weeks) readout and submission in 2024; full data will be presented at upcoming medical meetings

• If approved, remibrutinib has the potential to become the first of a new class of chronic spontaneous urticaria (CSU) treatment in a decade, offering a simple and effective option for the 60% of patients uncontrolled by H1-antihistamines2

Basel, August 09, 2023 — Novartis today announced positive top-line results from the Phase III REMIX-1 and REMIX-2 studies evaluating remibrutinib 25 mg b.i.d., a Bruton’s tyrosine kinase (BTK) inhibitor, in patients with chronic spontaneous urticaria (CSU) whose symptoms are inadequately controlled by H1-antihistamines¹. Both Phase III studies met their primary endpoint of absolute change from baseline in weekly urticaria activity score (UAS7) at Week 12, demonstrating clinically meaningful and statistically significant improvements in disease activity¹. The studies will continue until Week 52. Remibrutinib also demonstrated a rapid onset of action as illustrated by the improvement of UAS7 at Week 2 in the REMIX-1 and REMIX-2 studies¹. These data support the potential of remibrutinib as a new, effective and fast-acting oral treatment option for those uncontrolled by first-line H1-antihistamines¹.

“CSU is a distressing and unpredictable disease, and patients urgently need effective, convenient and well-tolerated treatments that can provide rapid and sustained relief from the relentless itching and deep tissue swelling that greatly impact their daily lives,” said Shreeram Aradhye, M.D., President, Global Drug Development and Chief Medical Officer, Novartis. “These positive top-line results from the Phase III REMIX studies confirm that remibrutinib, a highly selective BTK inhibitor, has the potential to be a first-in-class, oral treatment for people living with CSU whose symptoms are refractory despite use of antihistamines.”

CSU is the medical term for chronic hives that last for 6 weeks or longer, where the underlying cause is internal rather than external exposure to any allergen^3,4. Affecting 40 million people worldwide, CSU is characterized by itchy hives (wheals) and/or deep tissue swelling (angioedema), which can occur on the face, throat, hands and feet^3–6. Patients may experience burning, stinging and soreness on the skin where hives occur, causing a severe impact on their quality of life^2,3,7,8.

H1-antihistamines are the first-line treatment in CSU². Approximately 60% of patients are inadequately controlled with antihistamines alone and continue to live with the distressing symptoms of CSU². While injectable biologic therapies are an effective option for those whose CSU is uncontrolled by antihistamines, less than 20% of patients worldwide are treated with them¹. BTK is an enzyme central to the release of histamine, and when spontaneously activated plays a critical role in the debilitating symptoms associated with CSU⁹.

Discovered and developed by Novartis, remibrutinib is a highly selective oral BTK inhibitor that has the potential to provide rapid, sustained control of CSU within 2 weeks of initiation. It continues to show a favorable safety profile across several immune-mediated conditions including multiple sclerosis, hidradenitis suppurativa and food allergy^10–13. Patients currently enrolled in REMIX-1 and REMIX-2 will continue to receive treatment up to Week 52 and will have the opportunity to continue in a long-term extension trial^14,15.

Novartis will present the REMIX data at an upcoming medical meeting and intends to submit to global health authorities starting in 2024.

About remibrutinib
Remibrutinib is a highly selective, oral Bruton’s tyrosine kinase (BTK) inhibitor that blocks the BTK cascade and prevents the release of histamine that causes itch, hives/welts and swelling^9,16. In Phase II studies, remibrutinib demonstrated fast onset of action and sustained efficacy in patients with moderate to severe chronic spontaneous urticaria (CSU)⁹. Remibrutinib has been shown to be well-tolerated across all doses studied in Phase II⁹. These results have now been confirmed by the Phase III REMIX data¹. In addition to CSU, remibrutinib is being investigated in other immune-mediated conditions, such as multiple sclerosis, hidradenitis suppurativa, food allergy and Sjögren's syndrome^10–13,17. If approved, remibrutinib has the potential to become an effective oral option to complement Xolair^® (omalizumab), the first and only injectable biologic indicated for CSU¹⁸. In the US, Novartis Pharmaceuticals Corporation and Genentech, a member of the Roche Group, work together to develop and co-promote Xolair.

About REMIX-1 and REMIX-2
REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) are two identically designed global, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III studies, with REMIX-1 consisting of 470 participants and REMIX-2 consisting of 455 participants^14,15. Both studies are designed to establish the efficacy, safety and tolerability of remibrutinib in adult participants with chronic spontaneous urticaria that is inadequately controlled by second generation H1-antihistamines compared with placebo^14,15. The primary outcome measures include absolute change from baseline in the weekly urticaria activity score, absolute change in itch severity score and hive severity score at Week 12^14,15. Patients currently enrolled in REMIX-1 and REMIX-2 will continue to receive treatment up to Week 52 and will have the opportunity to continue in a long-term extension trial^14,15.

About chronic spontaneous urticaria (CSU)
CSU affects approximately 40 million people worldwide^4,5. CSU is characterized by the sudden appearance of itchy hives (wheals) and/or deep tissue swelling (angioedema) for more than 6 weeks, affecting all ages but most frequently between 20–40 years, with women affected nearly twice as often as men^3,4. CSU causes significant emotional distress, with the majority of patients suffering from sleep deprivation, and high rates of mental disorders, such as anxiety or depression⁴. There are currently limited effective treatment options for CSU, with many patients not achieving full control from the first-line treatment, antihistamines^2,3,7.